Stringent demands are placed on automatic analysis devices, especially in large-scale laboratories in which a high sampling rate must be permitted. Here, the analysis devices must be able to deal with a large number of reaction vessels with different samples and must be able to allocate these to different reagent containers. In this connection, pipetting devices, inter alia, are used to permit analysis of a sample by addition of the corresponding reagents and also further sample processing steps. Thus, with fully automatic treatment of reagents and samples, even labour-intensive analysis procedures can be performed reliably and quickly without requiring the involvement of specialized personnel for specialized analysis procedures. A demand placed on a fully or partially automated analysis procedure is, for example, the handling of sample quantities of different sizes which require a corresponding quantity of reagents. A fully automatic analysis system has to satisfy a wide variety of requirements. There are analysis systems with a high throughput and others with a low throughput, as are outlined in brief below.
In analysis systems for low throughputs of reagents, the cycle time for liquid removal is approximately 4 to 10 seconds, with the pipetting needle piercing the vessel lid upon each removal. The reagent cartridge has a relatively long dwell time on the device because of the low throughput. The dwell time is extended still further if the reagent cartridge contains seldom used reagents which are not often called upon and which accordingly can remain for up to 4 weeks in the analysis system with low throughputs. In these reagent cartridges, there is a need for a high level of protection against evaporation.
In analysis systems distinguished by a high throughput of reagents, there is generally a short cycle time of between 1 and 4 seconds for the pipetting and the positioning of reagent rotor and pipetting needle. Because of the short cycle time, piercing of the funnels with the pipetting needle is not possible. Because of the high throughput of reagents, the dwell time of the respective reagent cartridges on such analysis systems is only one to two days, for which reason evaporation from an opened flask can be tolerated here.
The handling of very small volumes is described, for example, in EP 0 504 967. Said document discloses reagent containers which permit the removal of small volumes and in which evaporation or aging of the remaining fluid in the container during further processing steps is avoided.
For this purpose, the reagent container has a suitably designed lid which, on one hand, is suitable for removal of liquid and, on the other hand, suppresses evaporation of the contents of the container. The lid has, in the middle of its base, a circular opening which is directed into the lid interior and opens out in a conical tip. For removing a sample, the tip of the cone is first pierced so that a pipetting needle, which is provided for removing very small sample quantities, can then be introduced into the vessel. When the reagent has been removed from the vessel, a small opening remains exclusively at the tip of the cylinder. After removal of the sample, the small opening at the cylinder tip of the lid also ensures that almost no liquid evaporates from the reagent container and that the content of the vessel does not undergo changes due to contact with, for example, atmospheric humidity or oxygen in the environment. Further details of this vessel closure can be taken from the prior art.
However, if a higher throughput and shorter processing times are to be achieved, the pipetting device, if it is to permit efficient handling of samples, must be equipped with correspondingly large pipetting tips to take up liquid. To ensure that in this case too the larger pipetting tips can still be inserted into the interior of the reagent vessel, a larger opening in the lid would be necessary.
In the prior art, many possible ways are described for producing openings in a closure of a reagent vessel. As is described in patents U.S. Pat. No. 6,255,101 and U.S. Pat. No. 3,991,896, this can be done by means of a ball being pushed through the shaft of a reagent vessel lid with the aid of a pin. The ball is pushed into the interior of the reagent container so that reagent liquid can then be removed through the shaft. Other possibilities, for example piercing a closure cap by means of a cannula as in document WO 83/01912, are likewise conceivable. The diameter of the opening can be chosen according to the size of the shaft or the cannula.
An alternative to an enlarged opening in a reagent closure involves removing the lid of the reagent containers prior to use.
In the prior art, this type of sample handling is used, for example, in analysis systems in the field of clinical-chemical analysis of biological samples. To remove a desired quantity of liquid reagent, the reagent is removed from the open reagent container and is transferred by means of an automatic pipetting device into a reaction cuvette. For each pipetting procedure, an electromechanically driven arm of the pipetting device is guided to an open reagent container so that handling of samples can take place in the desired manner. The content of a standard reagent container in this case suffices for a large number of pipetting procedures. In this connection, it has been found that fluid evaporates during the analysis method before it can be completely used up, on one hand through the removal of the reagent closure and on the other hand through the creation of a large opening in a closure cap. Especially in rooms with low atmospheric humidity, considerable amounts of the reagent solution are often lost through evaporation. One consequence of this is that the evaporation causes an increase in the concentration of the reagent in the fluid. By contrast, the volume of the reagent solution increases when using open reagent containers in rooms with relatively high atmospheric humidity, or through condensation water forming when cooled reagents are used so that the reagent concentration decreases over the course of time. Moreover, when open reagent containers are used, there is an exchange of gas with the surrounding air, which among other things causes aging of a reagent. Such effects on the reagent, in particular on the reagent concentration, result in a deterioration in the analysis precision. It has additionally been found that a removal of the reagent closure often has to be done manually. Under these circumstances, the laboratory personnel must take new reagent containers from their packaging and first of all remove the closure in order then to place the open reagent container in the analysis system in place of an empty reagent container. Since it often happens that many different reagents are needed at different times in one and the same analysis system, manual handling by laboratory personnel requires considerable labor. When reclosing the containers, it must additionally be ensured that the closures are not mixed up. In procedures carried out manually, the possible confusion of the closures represents a source of uncertainty.
In the prior art, therefore, methods are described which permit automatic removal of a reagent container closure. The document EP 0 930 504 discloses a lid-gripping device which is intended for automatic handling of a lid on sample vessels. The lid of the sample vessels in this case has a spike around which the lid-gripping device can grip. By means of a chuck, the lid is held so securely that, when the lid-gripping device is lifted, the lid is completely detached from the vessel, while a holding-down sleeve holds the vessel down to prevent lifting of the vessel.
The document U.S. Pat. No. 5,846,489 likewise discloses an automatic system for opening reagent vessels. Here, a pin of a gripping device is inserted into a groove provided for this purpose in the lid. At one end, the pin has a bead which allows the pin to be clamped in the groove of the lid. The lid can then be removed from the reagent vessel by lifting the pin.
Moreover, in U.S. Pat. No. 5,064,059, a device is described which allows a lid to be removed from the reagent vessel. However, the prior art described discloses only an automatic opening of reagent vessels closed by a stopper. Usually, stoppers are only used to close test tubes in which, for example, blood or another liquid from the human or animal body is received, but not reagent vessels. A disadvantage of the prior art is in this case that the mechanisms described do not permit opening of a screw-type closure of a reagent vessel. In practice, however, it has been found that, for reagent vessels which often contain a volatile fluid, a screwable closure is particularly suitable since such a screw-type closure guarantees a reliable sealing of the vessel.
In the prior art, U.S. Pat. No. 6,216,340 describes the removal of a reagent closure which is secured on the vessel by screwing. In this case, opener and reagent lid interact in the manner of a bayonet closure. Through a guide groove formed in the reagent closure, the automatic opener can insert a pin along the guide groove by rotation into the lid until this is mounted against a limit stop of the guide groove. If the rotational movement is continued in this direction, turning the lid off from the reagent vessel is possible. By rotating the opener in the opposite direction, the connection between lid and opener is released again. A disadvantage of the prior art is the fact that a precise production of the bayonet closure on the lid is an essential requirement for ensuring the functional reliability of the system. The screwing operation, after filling of the vessel, must guarantee a narrowly tolerated angle position of the bayonet closure and also have a good sealing effect.
Moreover, the opener must be guided with precision to the respective reagent vessel to permit engagement of the pin of the opener in the bayonet closure. This requires either a precise placement of the reagent vessels in the analysis system or a detection of position by the analysis system for the respective reagent vessel. Moreover, complex tools are needed for producing the reagent lid, with the result that the production costs are increased. Particularly in the case of reagent vessels handled as disposable articles, this is a considerable disadvantage. Before the opener, after removal of a first lid, can be used again to open reagent vessels, the lid additionally has to be removed from the opener. In the example described, additional measures are needed to do this, which measures permit rotation of the lid in the opposite direction so that the lid can be removed from the opener.